20% of American deaths every year have been reported to be caused by cancer-related diseases. For treatment of these cancers, chemotherapy is usually used, but few anticancer drugs have been known to be effective.
Most of deaths caused by cancer stem from the metastasis of cancer rather than the first occurrence of cancer itself. (Fifler, 1991 cancer metastasis. Br. Med. Bull. 47, 157-177). By many experiments and clinical tests, it was confirmed that the natural immunity plays an important role in inhibiting the cancer metastasis and destroying a cancer itself (Schantz et al., cancer immunol. Immunother. 25., 141-148, 1987).
NKT (Natural Killer T) cells are a specialized population of α/β T cells that coexpress receptors of the NK lineage and have the unique potential to secrete very rapidly the large amount of cytokines providing early help for effector cells and regulating the Th1 or Th2 differentiation of some immune responses (Annu. Rev. Immunol. 1997. 15; Albert Bendelae et al. p 535). Moreover, they also eliminate infectious germs or bacteria such as cancer cells, parasites, listerias, tuberculoses, and so on (Seki et al., Clin. Immunol., 28, p 1069, 1996).
NK cells, LAK cells and macrophages, in addition to the NKT cells, are known to be cells that can effectively inhibit infection by cancer cells, viruses, and bacteria. More particularly, the effective activation of NK cells, LAK cells and macrophages has been known to block the cancer cell growth and its metastasis. Also, the activation of NK cells by immune stimulators has been reported to inhibit the cancer cell proliferation caused by cancer metastasis (Herberman, 1984 J. invest. Dermatol. 83, 137-140).
These anticancer, anti-metastasis and anti-virus functions of the immune system are mediated by the secretion of various kinds of cytokines, activating the immune system. Especially, gamma interferon, tumor necrosis factor-alpha, etc. are the representative cytokines associated with anticancer, anti-metastasis and anti-virus functions.
Gamma interferon, which is mainly generated by T cells, serves to control the immune reaction and also activate T and B cells, neutrophils, NK cells, and macrophages to make them attack cancer cells. Therefore, Gamma interferon is used as a treatment for chronic bone marrow leukemia and kidney cancer. Moreover, Gamma interferon has a strong inhibitory effect on DNA replication and cell proliferation, so that it is also clinically applied to not only cancer treatment but also to treat virus infection, multi-resistance bacteria and fungi infection, by suppressing the proliferation of microorganisms.
Tumor necrosis factor-alpha is mainly generated by macrophages and is involved in various immune reactions such as the inflammatory reaction, and especially shows a very strong toxicity to cancer cells. At present, TNF-alpha is on the verge of approval as a skin cancer treatment in Japan, pending clinical test results.
However, using cytokines directly for anticancer therapy brings unexpected side effects, such as an inflammatory reaction, emesis and so on. Therefore, many trials are being made to find materials that can wholly activate the immune system, rather than using only a particular cytokine.
Regretfully, few natural products are known to activate immune cells including NK cells: for example, a lectin from Viscum coloratum extraction, which is partially used as a substitute therapy for a cancer treatment, and polysaccharides belonging to beta-glucan series obtained from a mushroom.
Meanwhile, plants belonging to Panax genus (so-called, “ginseng”), as a representative tonic medicine, are usually used in the form of white ginseng, being dried at room temperature after harvest, or in the form of red ginseng, being heat-treated after harvest. Much research has been performed to characterize the ingredients and medical effects of ginseng, and the reported medical effects include, aging inhibition, anti-artherosclerosis, hyperlipidemia remedy, enhancement of liver function, elimination of irradiation side effects, immune system enhancement, anti-thrombus, increase of brain function, anti-stress, blood sugar decrease, blood pressure decrease, and anticancer effects. The major ingredients inducing these effects have been found to belong to the saponin series. Recent research has focused on extraction/separation of acidic polysaccharides from the roots of ginseng so as to identify their effects. These acidic polysaccharides have been known to activate macrophages, thereby making the macrophages expedite the generation of interferon-gamma and thus inhibiting proliferation of cancer cells (Korean Patent No. 144130).
Most research so far has concentrated only on the roots of ginseng, but not on the leaves and stems of ginseng, except in some cases. While the roots of ginseng must be cultivated at least 6 years so as to exhibit a medicinal effect, the leaves and stems of ginseng are grown every year and then wasted. Accordingly, if it is found that the leaves or stems of ginseng contain specific physiologically active ingredients as the ginseng roots do, it will be a great merit in view of the use of by-products and environmental care.
As mentioned above, use of the leaves and stems of ginseng has been limited to some cases: the production of cosmetics by using saponin of ginseng leaves (Korean Patent Laid-open No. 81-3736), the method of obtaining aglycon saponin from ginseng leaves under alkali conditions (Korean Pharmaceutical Bulletin, 38(4), 1994, 8), the preparation of a shampoo and lotion by using extracts of herbs including ginseng leaves (Korean Patent No. 23641), and the preparation of a clean tissue for women containing ginseng leaves (Korean Patent No. 214223).
Some research has shown that the polysaccharides obtained from the leaves of ginseng are effective for gastric ulcer treatment (Planta Med. 58, 1992, 445-448); however, no research suggests that the extract from the leaves or stems of ginseng has an anticancer effect, cancer metastasis inhibition, etc.